Research Themes for PhD Training

Structural Biology

The Structural Studies Group uses the four complementary techniques of X-ray protein crystallography, of nuclear magnetic resonance spectroscopy (NMR), of cryo-electron microscopy (cryoEM), and of bioinformatics to explore systems of fundamental and medical importance in atomic detail.

The X-ray crystallography group explores the structures of macromolecules in the highest level of atomicl detail with. Major areas of interest are: DNA and RNA binding proteins; Enzyme stability, specificity, and activity; Anti-infective discovery programmes ; and Structural genomics/ proteomics.

The NMR group researches on the structures of proteins in solution, with particular emphases on their dynamic behaviour and how they assemble into their complex folds. Protein mis-folding in disease states such as Alzheimers Disease and CJD is an important part of this research.

The Electron microscopy group focuses on two challenging areas of structural biology - membrane proteins and very large macromolecular complexes. Our main technique is high resolution cryoelectron microscopy which we often use to complement other structural techniques such as X-ray crystallography.

The Bioinformatics group is concerned with investigating and exploiting the vast amount of information now available on biological macromolecules. In collaboration with information and computer scientists we are focussing on methods to make the best possible use of the three-dimensional information obtained by the other structural techniques.

Cell Biology and Genetics

Cell Biology and Genetics are major fields in modern molecular biology. These fields encompass research aimed at discovering the detail of how cells grow and divide and how gene products interact to create a phenotype. In our department the various Cell Biology and Genetics research groups use model organisms to investigate fundamental biological questions that are of paramount importance to human health or developing useful biotechnology. These include fungal pathogenesis, apoptosis (programmed cell death), membrane trafficking, organelle inheritance, cell differentiation, mRNA export, adaptation to stress, genome stability, chromosome dynamics, and chromosome and nuclear architecture.

The Department is a partner in the Centre for Stem Cell Biology whose research provides a focus for the development of Human Embryonic Stem (ES) Cell technologies and resources that are central to the long term goal of developing clinical applications of stem cells in regenerative medicine. The Centre has extensive experience in the culture, characterisation and biology of human ES cells and their malignant counterpart embryonal carcinoma cells and uses high throughput technologies such as proteomics and microarrays to investigate the factors controlling stem cell differentiation, the mechanisms of pluripotency, and the maintenance of genetic stability. Tissue engineering techniques are used to transform cultured cells into useful tissue.

Biochemistry and Genomics

Contemporary Biochemistry is carried out against the backdrop of information generated by global efforts in whole genome sequencing which has seen the complete sequencing of plant, bacterial and human genomes. The classical one gene-one enzyme approach to the study and investigation of the chemistry of living processes has been transformed in the last few years by the drive to understand molecular interactions of the cell in an holistic manner. By combining the power of molecular genetics and sensitive physical methods, it is now possible to determine not only structure function relationships of individual protein molecules, but to consider the interplay between proteins in large highly regulated assemblies and the pathways in which they operate. At Sheffield we have built parallel state of the art capabilities in structural and functional molecular biology to provide a rich environment for 21st century Biochemistry. The Department of Molecular Biology and Biotechnology provides the breadth and depth needed to meet the successful challenges of post genomic science in areas stretching from molecular structure determination to the molecular and cellular aspects of photosynthesis, gene regulation and cellular defence pathways.

Molecular Microbiology

Microbiology in Sheffield is a core theme. We use multidisciplinary approaches to understand the fundamental principles governing the life of bacteria and their interaction with the environment. For pathogens this environment is the host and our work is leading to potential novel approaches for control. The research is in three main areas.

Molecular microbial physiology: How bacteria are able to adapt to changing and stressful environments to allow them to survive and proliferate. Research projects include oxidative stress resistance, differentiation, aerobic/anaerobic switch etc.

Microbial pathogenesis: The burden of human disease is great and in some cases increasing due to the spread of antibiotic resistance. Research projects include Staphylococcus aureus (MRSA, vaccine development, novel drug targets, host/pathogen interaction etc.), Campylobacter jejuni (food poisoning, colonization factors, in vivo metabolism etc.), Helicobacter jejuni (ulcers, metabolic capabilities etc.), Salmonella typhimurium (stress resistance, regulation of virulence factors etc.).

Environmental microbiology: Bacteria are able to live in some of the most hostile and toxic environments on earth. Research projects include salt tolerance and bioremediation.